An mRNA vaccine in a pill?

mRNA pills are here.

All available mRNA vaccines are currently injection-only. While there are plenty of logical reasons to inject vaccines, this can present a serious obstacle for people with phobias of needles.

A group of US researchers have developed a swallow-able mRNA capsule. In addition to paving the way for edible mRNA COVID vaccines, they say their discovery could also help to treat gastrointestinal disorders.

The researchers, who are based at the Massachusetts Institute of Technology (MIT), US, had previously developed a capsule that could place solid drugs in people’s stomach lining.

Now, they’ve been able to show that the same capsule could also deliver RNA and DNA. They’ve published their findings in the journal Matter.

“Nucleic acids, in particular RNA, can be extremely sensitive to degradation particularly in the digestive tract,” says co-author and gastroenterologist Dr Giovanni Traverso.

“Overcoming this challenge opens up multiple approaches to therapy, including potential vaccination through the oral route.”

The capsule, which is roughly a centimetre in size, has a steep dome inspired by the leopard tortoise. This allows the capsule to right itself in the stomach, then settling on the stomach lining and releasing its drug.

In injectable vaccines, the mRNA is typically coated by fatty molecules called lipids to prevent it from degrading in the body. It’s referred to as a lipid nanoparticle coating, because the lipids and mRNA become blobs that are a few nanometres in size.

These researchers tried a slightly different method of coating, using polymers called poly(beta-amino esters). They’d previously shown that a sub-class of these polymers – branched polymers – were better at delivering drugs to the body.

“We made a library of branched, hybrid poly(beta-amino esters), and we found that the lead polymers within them would do better than the lead polymers within the linear library,” says co-author Dr Ameya Kirtane.

“What that allows us to do now is to reduce the total amount of nanoparticles that we are administering.”

The researchers have tested their capsules on the stomachs of mice and pigs, showing that they could deliver RNA in both cases. They were able to deliver 150 micrograms of RNA to pig stomachs – more than the 30–100 micrograms of mRNA in commercial COVID vaccines.

While injections work fine for COVID mRNA vaccines, the researchers are interested to see if mRNA pills could provide an alternative. They’re also keen to test the treatment for diseases that don’t respond as well to injection.

“When you have systemic delivery through intravenous injection or subcutaneous injection, it’s not very easy to target the stomach,” says co-author Dr Alex Abramson.

“We see this as a potential way to treat different diseases that are present in the gastrointestinal tract.”